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Resting-state prefrontal EEG biomarkers in correlation with MMSE scores in elderly individuals.

ABSTRACT: We investigated whether cognitive decline could be explained by resting-state electroencephalography (EEG) biomarkers measured in prefrontal regions that reflect the slowing of intrinsic EEG oscillations. In an aged population dwelling in a rural community (total?=?496, males?=?165, females?=?331), we estimated the global cognitive decline using the Mini-Mental State Examination (MMSE) and measured resting-state EEG parameters at the prefrontal regions of Fp1 and Fp2 in an eyes-closed state. Using a tertile split method, the subjects were classified as T3 (MMSE 28-30, N?=?162), T2 (MMSE 25-27, N?=?179), or T1 (MMSE???24, N?=?155). The EEG slowing biomarkers of the median frequency, peak frequency and alpha-to-theta ratio decreased as the MMSE scores decreased from T2 to T1 for both sexes (-5.19???t-value???-3.41 for males and -7.24???t-value???-4.43 for females) after adjusting for age and education level. Using a double cross-validation procedure, we developed a prediction model for the MMSE scores using the EEG slowing biomarkers and demographic covariates of sex, age and education level. The maximum intraclass correlation coefficient between the MMSE scores and model-predicted values was 0.757 with RMSE?=?2.685. The resting-state EEG biomarkers showed significant changes in people with early cognitive decline and correlated well with the MMSE scores. Resting-state EEG slowing measured in the prefrontal regions may be useful for the screening and follow-up of global cognitive decline in elderly individuals.

SUBMITTER: Choi J

PROVIDER: S-EPMC6639387 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Resting-state prefrontal EEG biomarkers in correlation with MMSE scores in elderly individuals.

Choi Jungmi J Ku Boncho B You Young Gooun YG Jo Miok M Kwon Minji M Choi Youyoung Y Jung Segyeong S Ryu Soyoung S Park Eunjeong E Go Hoyeon H Kim Gahye G Cha Wonseok W Kim Jaeuk U JU

Scientific reports 20190718 1

We investigated whether cognitive decline could be explained by resting-state electroencephalography (EEG) biomarkers measured in prefrontal regions that reflect the slowing of intrinsic EEG oscillations. In an aged population dwelling in a rural community (total = 496, males = 165, females = 331), we estimated the global cognitive decline using the Mini-Mental State Examination (MMSE) and measured resting-state EEG parameters at the prefrontal regions of Fp1 and Fp2 in an eyes-closed state. Usi ...[more]

PMID: 31320666

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Project description:In this paper, we explore the utility of resting-state EEG measures as potential biomarkers for the detection and assessment of cognitive decline in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Neurophysiological biomarkers of AD derived from EEG and FDG-PET, once characterized and validated, would expand the set of existing diagnostic molecular biomarkers of AD pathology with associated biomarkers of disease progression and neural dysfunction. Since symptoms of AD often begin to appear later in life, successful identification of EEG-based biomarkers must account for age-related neurophysiological changes that occur even in healthy individuals. To this end, we collected EEG data from individuals with AD (n = 26), MCI (n = 53), and cognitively normal healthy controls stratified by age into three groups: 18-40 (n = 129), 40-60 (n = 62) and 60-90 (= 55) years old. For each participant, we computed power spectral density at each channel and spectral coherence between pairs of channels. Compared to age matched controls, in the AD group, we found increases in both spectral power and coherence at the slower frequencies (Delta, Theta). A smaller but significant increase in power of slow frequencies was observed for the MCI group, localized to temporal areas. These effects on slow frequency spectral power opposed that of normal aging observed by a decrease in the power of slow frequencies in our control groups. The AD group showed a significant decrease in the spectral power and coherence in the Alpha band consistent with the same effect in normal aging. However, the MCI group did not show any significant change in the Alpha band. Overall, Theta to Alpha ratio (TAR) provided the largest and most significant differences between the AD group and controls. However, differences in the MCI group remained small and localized. We proposed a novel method to quantify these small differences between Theta and Alpha bands' power using empirically derived distributions of spectral power across the time domain as opposed to averaging power across time. We defined Power Distribution Distance Measure (PDDM) as a distance measure between probability distribution functions (pdf) of Theta and Alpha power. Compared to average TAR, using PDDF enhanced the statistical significance, the effect size, and the spatial distribution of significant effects in the MCI group. We designed classifiers for differentiating individual MCI and AD participants from age-matched controls. The classification performance measured by the area under ROC curve after cross-validation were AUC = 0.85 and AUC = 0.6, for AD and MCI classifiers, respectively. Posterior probability of AD, TAR, and the proposed PDDM measure were all significantly correlated with MMSE score and neuropsychological tests in the AD group.

Project description:Functional and effective connectivity are known to change systematically over time. These changes might be explained by several factors, including intrinsic fluctuations in activity-dependent neuronal coupling and contextual factors, like experimental condition and time. Furthermore, contextual effects may be subject-specific or conserved over subjects. To characterize fluctuations in effective connectivity, we used dynamic causal modelling (DCM) of cross spectral responses over 1- min of electroencephalogram (EEG) recordings during rest, divided into 1-sec windows. We focused on two intrinsic networks: the default mode and the saliency network. DCM was applied to estimate connectivity in each time-window for both networks. Fluctuations in DCM connectivity parameters were assessed using hierarchical parametric empirical Bayes (PEB). Within-subject, between-window effects were modelled with a second-level linear model with temporal basis functions as regressors. This procedure was conducted for every subject separately. Bayesian model reduction was then used to assess which (combination of) temporal basis functions best explain dynamic connectivity over windows. A third (between-subject) level model was used to infer which dynamic connectivity parameters are conserved over subjects. Our results indicate that connectivity fluctuations in the default mode network and to a lesser extent the saliency network comprised both subject-specific components and a common component. For both networks, connections to higher order regions appear to monotonically increase during the 1- min period. These results not only establish the predictive validity of dynamic connectivity estimates - in virtue of detecting systematic changes over subjects - they also suggest a network-specific dissociation in the relative contribution of fluctuations in connectivity that depend upon experimental context. We envisage these procedures could be useful for characterizing brain state transitions that may be explained by their cognitive or neuropathological underpinnings.

Project description:ObjectiveWe evaluated the value of resting-state EEG source biomarkers to characterize mild cognitive impairment (MCI) subjects with an Alzheimer's disease (AD)-like cerebrospinal fluid (CSF) profile and to track neurodegeneration throughout the AD continuum. We further applied a resting-state functional MRI (fMRI)-driven model of source reconstruction and tested its advantage in terms of AD diagnostic accuracy.MethodsThirty-nine consecutive patients with AD dementia (ADD), 86 amnestic MCI, and 33 healthy subjects enter the EEG study. All ADD subjects, 37 out of 86 MCI patients and a distinct group of 53 healthy controls further entered the fMRI study. MCI subjects were divided according to the CSF phosphorylated tau/β amyloid-42 ratio (MCIpos: ≥ 0.13, MCIneg: < 0.13). Using Exact low-resolution brain electromagnetic tomography (eLORETA), EEG lobar current densities were estimated at fixed frequencies and analyzed. To combine the two imaging techniques, networks mostly affected by AD pathology were identified using Independent Component Analysis applied to fMRI data of ADD subjects. Current density EEG analysis within ICA-based networks at selected frequency bands was performed. Afterwards, graph analysis was applied to EEG and fMRI data at ICA-based network level.ResultsADD patients showed a widespread slowing of spectral density. At a lobar level, MCIpos subjects showed a widespread higher theta density than MCIneg and healthy subjects; a lower beta2 density than healthy subjects was also found in parietal and occipital lobes. Evaluating EEG sources within the ICA-based networks, alpha2 band distinguished MCIpos from MCIneg, ADD and healthy subjects with good accuracy. Graph analysis on EEG data showed an alteration of connectome configuration at theta frequency in ADD and MCIpos patients and a progressive disruption of connectivity at alpha2 frequency throughout the AD continuum.ConclusionsTheta frequency is the earliest and most sensitive EEG marker of AD pathology. Furthermore, EEG/fMRI integration highlighted the role of alpha2 band as potential neurodegeneration biomarker.

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Resting-state prefrontal EEG biomarkers in correlation with MMSE scores in elderly individuals.

Publications

Resting-state prefrontal EEG biomarkers in correlation with MMSE scores in elderly individuals.

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